Excitation-contraction coupling and relaxation in porcine carotid arteries are specifically dependent on glucose

Abstract

Vascular metabolism is compartmentalized, such that aerobic glycolysis is associated with membrane energy-dependent functions and oxidative metabolism correlates with vascular contractility. We investigated the importance of glucose, a primary substrate for glycolysis, in maintenance of resting tension and excitation-contraction (EC) coupling in porcine carotid artery. All arteries were precontracted with 80 mM KCl and exposed to hypoxia in the absence of glucose (6 min) to deplete stored glycogen, an alternative substrate for glycolysis. After depletion, sensitivity to agonists was substantially increased. The concentration of norepinephrine (NE) that induced half-maximal response (EC50) was significantly decreased under glucose-free conditions, and the maximal response was unchanged. The decrease in EC50, or increase in sensitivity, was reversed by glucose, but not by beta-hydroxybutyrate, a substrate for oxidative metabolism. Similar results were obtained in concentration-isometric force responses of histamine and KCl. Importantly, measurements of high-energy phosphagen content in freeze-clamped arteries indicate that these substrate perturbations were not associated with significant changes in global energy stores. Responses to a single dose of NE or histamine in Ca(2+)-free medium were significantly lower if intracellular Ca2+ stores were loaded in the presence of beta-hydroxybutyrate than in the presence of glucose, suggesting that normal maintenance of intracellular Ca2+ stores also depends specifically on glucose. Furthermore 14 of 26 rings exhibited an increase in resting tension and/or oscillation in the absence of glucose, despite near-normal force responses to KCI. This phenomenon was reversed by nifedipine or glucose.(ABSTRACT TRUNCATED AT 250 WORDS)